Lymphocytic choriomeningitis virus: an under-recognized arenaviral threat with important maternal–fetal implications

Lymphocytic choriomeningitis virus (LCMV), a rodent-borne arenavirus first identified in 1933, remains a neglected zoonotic pathogen of growing recognition in urban, non-endemic regions. Although typically associated with rural rodent exposure, recent epidemiological data indicate substantial circulation in cities, particularly affecting pregnant women and leading to severe congenital infections. This comprehensive review examines the evolving epidemiology, clinical spectrum, diagnostic challenges, and public health implications of LCMV, with special emphasis on congenital disease. Recent seroprevalence studies, most notably the 2026 Philadelphia study, reported immunoglobulin G (IgG) seropositivity rates of 2.4–2.7% among urban pregnant women, with exposure strongly linked to neighborhood deprivation indices, substandard housing, and socioeconomic vulnerability. Comparable patterns of continued circulation have been documented across Europe (Germany, Hungary, Bulgaria), Australia, Brazil, and with the identification of a novel, more virulent strain in New Mexico, United States. These findings challenge the traditional view of LCMV as a low-risk rural pathogen and highlight the roles of urbanization, climate change, global migration, and improved molecular diagnostics (reverse transcription polymerase chain reaction [RT-PCR] and metagenomic next-generation sequencing [mNGS]) in its changing epidemiology. Congenital LCMV infection can result in devastating fetal outcomes characterized by the classic tetrad of chorioretinitis, hydrocephalus, microcephaly, and periventricular calcifications. Affected infants frequently experience significant long-term neurodevelopmental disabilities, including intellectual impairment, seizures, motor deficits, and sensory loss. The virus exhibits strong placental tropism, with timing of maternal infection critically influencing the severity of fetal brain injury. Fetal neuroimaging (serial ultrasound and magnetic resonance imaging [MRI]) plays a central role in diagnosis and prognosis. This review provides an in-depth analysis of diagnostic modalities, including RT-PCR, mNGS, and serological testing (immunoglobulin M [IgM]/IgG), along with their respective strengths, limitations, and optimal timing. A practical risk-stratified prenatal screening algorithm and serial fetal neuroimaging protocol are proposed. Current therapeutic options are limited to supportive care, as no approved specific antivirals are safe for use in pregnancy. Prevention strategies, travel medicine considerations for pregnant travelers, and guidance for migrant populations are also addressed. In the era of rapid urbanization and global connectivity, LCMV exemplifies an under-recognized arenaviral pathogen capable of causing significant maternal–fetal morbidity. Increased clinical awareness, enhanced surveillance, targeted screening in high-risk groups, and investment in antiviral and vaccine development are urgently required to reduce the burden of this neglected congenital infection.